Solute concentration measurement device and related methods

ABSTRACT

A solute concentration measurement device is disclosed. The device may comprise a filter membrane, an exchange chamber, a sensing chamber, a separator, and a sensor. The device may be configured to be placed in fluid communication with a sample solution containing a solute and a solvent. The filter membrane may provide selective fluid communication between the solution and the exchange chamber. The separator may separate the exchange chamber from the sensing chamber and cause a change in a condition of the sensing chamber corresponding to a change of a condition of the exchange chamber. The sensor may sense the condition pertaining to the sensing chamber and calculate the concentration of the sample solution corresponding to this change.

RELATED APPLICATIONS

This application claims the Paris Convention Priority of andincorporates by reference U.S. Provisional Application No. 61/098,655,filed Sep. 19, 2008, and U.S. Provisional Application No. 61/102,776,filed Oct. 3, 2008.

BACKGROUND

This disclosure relates generally to devices and methods fordetermination of an unknown solute concentration in a solution. Inparticular, the present disclosure relates to determining theconcentration of a solute, such as glucose, in the body fluids, such asinterstitial fluid or bloodstream, of a patient who requires monitoringof such concentration for medical purposes.

SUMMARY

A solute concentration measurement device is disclosed. The device maycomprise a filter membrane, an exchange chamber, a sensing chamber, aseparator, and a sensor. The device may be configured to be placed influid communication with a sample solution containing a solute and asolvent. The filter membrane may provide selective fluid communicationbetween the solution and the exchange chamber. The separator mayseparate the exchange chamber from the sensing chamber and cause achange in a condition of the sensing chamber corresponding to a changeof a condition of the exchange chamber. The sensor may sense thecondition pertaining to the sensing chamber and calculate theconcentration of the sample solution corresponding to this change.

According to features of the present disclosure, A device comprising, incombination a housing having disposed therein a filter membrane, anexchange chamber, and a sensing chamber having disposed therein apressure sensor. The exchange chamber and sensing chamber are separatedby a separator. The device is adapted to measure the concentration of asolute in a sample solution. The solute is glucose.

According to features of the present disclosure, a method is disclosedcomprising, in combination providing an exchange chamber, a sensingchamber, a filter membrane configured to provide selective fluidcommunication between the sample solution and the exchange chamber, butis substantially impermeable to a solute contained in the exchangechamber, a movable separator configured to separate the exchange chamberfrom the sensing chamber; and a sensor configured to sense a conditionpertaining to the sensing chamber. The device is adapted to be placedinto fluid communication with a sample solution.

According to features of the present disclosure, a method is disclosedcomprising placing a solute concentration measurement device comprisinga housing having disposed therein at least an exchange chamber, asensing chamber having a pressure sensor, a filter membranesubstantially impermeable to the solute, and a movable separator intofluid communication with a sample solution, measuring the pressure inthe sensing chamber after allowing a solute concentration in theexchange chamber to equilibrate with a solute concentration in thesample solution, and using the measured pressure in the sensing chamberto calculate the concentration of the solute in the sample solution.

DRAWINGS

The above-mentioned features and objects of the present disclosure willbecome more apparent with reference to the following description takenin conjunction with the accompanying drawings wherein like referencenumerals denote like elements and in which:

FIG. 1 is a schematic view of an embodiment of a solute concentrationmeasurement device;

FIG. 2 is a schematic view of an embodiment of a solute concentrationmeasurement device, prior to being placed in fluid communication with asample solution;

FIG. 3 is a schematic view of an embodiment of a solute concentrationmeasurement device, after being placed in fluid communication with asample solution;

FIG. 4 is a schematic view of an embodiment of a solute concentrationmeasurement device, being placed in fluid communication with a samplesolution of low concentration; and

FIG. 5 is a schematic view of an embodiment of a solute concentrationmeasurement device, being placed in fluid communication with a samplesolution of high concentration, according to one or more embodiments ofthe present disclosure.

DETAILED DESCRIPTION

In the following detailed description of embodiments of the presentdisclosure, reference is made to the accompanying drawings in which likereferences indicate similar elements, and in which is shown by way ofillustration specific embodiments in which the present disclosure may bepracticed. These embodiments are described in sufficient detail toenable those skilled in the art to practice the present disclosure, andit is to be understood that other embodiments may be utilized and thatlogical, mechanical, electrical, functional, and other changes may bemade without departing from the scope of the present disclosure. Thefollowing detailed description is, therefore, not to be taken in alimiting sense, and the scope of the present disclosure is defined onlyby the appended claims. As used in the present disclosure, the term “or”shall be understood to be defined as a logical disjunction and shall notindicate an exclusive disjunction unless expressly indicated as such ornotated as “xor.”

As used herein, the term “real time” shall be understood to mean theinstantaneous moment of an event or condition, or the instantaneousmoment of an event or condition plus short period of elapsed time usedto make relevant measurements, optional computations, etc., andcommunicate the measurement, computation, or etc., wherein the state ofan event or condition being measured is substantially the same as thatof the instantaneous moment irrespective of the elapsed time interval.Used in this context “substantially the same” shall be understood tomean that the data for the event or condition remains useful for thepurpose for which it is being gathered after the elapsed time period.

The inventors of the present disclosure have discovered devices andmethods for determining the concentration of a solute in a solution inreal time. Specifically, the concentration of glucose in the body fluidsmay be monitored by the devices and using the methods of the presentdisclosure in real time. The devices disclosed herein, may be long termimplantable devices, or devices that connect to ports that allow forfluid communication between the device and body fluids.

According to embodiments, FIG. 1 illustrates a solute concentrationmeasurement device 10. When used as a medical device, artisansappreciate the instant system as adjustable and configured to optimallysupport a patient's needs, as determined by qualified care providers.According to embodiments, device 10 is used to measure the concentrationof glucose in a patient's body fluids, such as interstitial fluid orblood, in real-time. FIG. 2 depicts the device 10 prior to beinginserted into a sample solution 30 and FIGS. 3-5 depict the deviceimmersed it the sample solution 30, with the solid vertical line in eachfigure representing a figurative boundary of an area containing thesample solution 30.

According to embodiments, device 10 includes housing 12, which enclosesexchange chamber 18 and sensing chamber 20. According to embodiments, atleast a portion of housing 12 includes filter membrane 14. Filtermembrane 14 separates exchange chamber 18 from sample solution 30.

According to embodiments, filter membrane 14 provides selective fluidcommunication between sample solution 30 and exchange chamber 18. Forexample, filter membrane 14 may be a selectively permeable membrane.According to embodiments, filter membrane 14 may permit unrestrictedpassage of the solvent of sample solution 30 across filter membrane 14,but prohibit passage of the solutes of sample solution 30 across filtermembrane 14. According to embodiments, filter membrane 14 is a thin filmcomposite membrane or osmotic membrane.

According to embodiments, exchange chamber 18 may contain an exchangesolution containing at least one solute as are found in sample solution30. According to embodiments, the solvent that moves across filtermembrane 14 is water. Filter membrane 14 allows free exchange of thesolvent, but prohibits passage of the solute common to sample solution30 and exchange chamber 18, thereby retaining the same number of solutemolecules in exchange chamber 18 and making possible the calculation ofthe concentration in exchange chamber 18. According to embodiments,exchange chamber 18 comprises a small volume compared to the volume ofsample solution 30 such that the process of equalizing the concentrationof exchange chamber 18 will not appreciably change the concentration ofsample solution 30.

According to embodiments, separator 16 divides exchange chamber 18 fromsensing chamber 20. Generally, separator 16 comprises a device thatallows exchange chamber 18 to increase or decrease in volume dependingon the volume of solvent in exchange chamber 18. Because the totalvolume of device 10 is fixed, the volume of exchange chamber 18 isinversely proportional to the volume of sensing chamber 20, asillustrated in FIGS. 3, 4, and 5.

Separator 16 comprises a piston or elastomeric membrane, for exampleArtisans will readily recognize devices that sealably separate exchangechamber 18 and sensing chamber 20, while allowing separator 16 to beadjusted whereby the volumes of exchange chamber 18 and sensing chamber20 are changed. Separator 16 responds to the change in volume ofexchange chamber 18 as solvent moves into or out of exchange chamber 18.For example, separator 16 may respond to an increase in the pressurewithin exchange chamber 18 relative to the pressure within sensingchamber 20 by increasing the volume of exchange chamber 18 anddecreasing the volume of sensing chamber 20 until equilibrium ofpressures occurs.

According to embodiments, housing 12 is rigid, such that the totalcombined volume of exchange chamber 18 and sensing chamber 20 isconstant. Thus, a change in the volume of exchange chamber 18 results ina corresponding, equal and opposite change in the volume of sensingchamber 20 to maintain the total combined volume of both. Sensingchamber 20 contains a compressible fluid that varies in pressure as aconsequence of any change in volume of sensing chamber 20. According toembodiments, sensing chamber 20 contains a compressible gas. The volumeand pressure of the gas changes as separator 16 varies in position.

According to embodiments, sensing chamber 20 may include pressure sensor22. Sensor 22 measures the pressure of the gas in sensing chamber 20.For example, sensor 22 may be a pressure transducer to measure thepressure within sensing chamber 20. According to embodiments, atemperature sensor may also be disposed in sensing chamber 20 to improvethe accuracy of the measurement.

According to embodiments, the distance separator 16 travels as itadjusts while exchange chamber 18 comes to equilibrium may be measured,allowing for a determination of the change in volume in sensing chamber20, thereby allowing the concentration of exchange chamber 18 to becalculated, as disclosed herein.

A computer performs the relevant calculations. The computer comprises atleast a timing device for measuring elapsed time, which may comprise aclock or a timer, for example; devices to receive input from thepressure sensors, temperature sensors, and users; and a processor forperforming the calculations disclosed herein.

According to embodiments, a method is disclosed herein for measuring theconcentration of sample solution 30. Solute concentration measurementdevice 10 is put in fluid communication with a sample solution 30,whereby at least filter membrane 14 is in fluid communication withsample solution 30. According to embodiments, sample solution 30includes a solute and a solvent. According to embodiments, samplesolution 30 is a fluid within a body of a patient requiring medicaltreatment relating to the concentration of a solute in sample solution30. According to embodiments, sample solution 30 comprises interstitialfluid; accordingly glucose is the solute.

The concentrations of sample solution 30 and exchange chamber 18equalize as the solvent moves across filter membrane 14. Accordingly,the concentrations of sample solution 30 and exchange chamber 18 willreach substantial equilibrium through the diffusion of the solventacross filter membrane 14. According to embodiments, a predeterminedtime period may need to elapse for the exchange chamber 18 to come intoequilibrium with sample solution 30.

According to other embodiments, allowing exchange chamber 18 to comeinto equilibrium is not necessary. Rather, prior to contact with samplesolution 30, one or more curves may be modeled from test samplesolutions of known concentration for a given period of time. The resultswill be a number of curves that illustrate pressure of sensing chamber20 versus concentration. Consequently, rather than waiting forestablishment of equilibrium, the concentration may be determined byfitting the change in concentration of exchange chamber 18 to a curve ofknown behavior.

According to embodiments, FIG. 4 shows an embodiment of a soluteconcentration measurement device in a sample solution of lowerconcentration than exchange chamber 18. When device 10 is placed intofluid communication across filter membrane 14, solvent, for examplewater, flows across filter membrane 14 until the concentrations ofexchange chamber 18 and sample solution 30 is substantially the same.

According to embodiments, the amount of solute in exchange chamber 18 isknown. Initially, a known volume of fluid is placed into exchangechamber 18 and a pressure measurement is taken with pressure sensor 22.Thus, the initial concentration of device 10 is determined prior toplacing it into contact with sample solution 30.

According to alternate embodiments, the concentration of sample solution30 is known. Because exchange chamber 18 is separated by filter membrane14, solvent may eventually cross over the membrane or solvent may belost, e.g., due to evaporation, whereby an initial calibration no longeraccurately represents the concentration of exchange chamber 18.

According to embodiments, recalibration solution may be provided wherebydevice 10 is recalibrated. The concentration of recalibration solutionis known and can be input into device 10. Device 10 is then placed influid communication with the recalibration solution across filtermembrane 14 and a recalibration command is given before or after theconcentrations of recalibration solution and exchange chamber 18 comeinto equilibrium. If given before, device 10 allows for a time periodfor equilibrium to occur. After equilibrium occurs, one or more pressuremeasurements will be taken and device 10 will thereafter have acorrected “base” concentration.

FIG. 5 shows embodiments of device 10 when it is placed in fluidcommunication of sample solution 30 of higher concentration than that ofexchange chamber 18, according to embodiments. Due to the osmoticpressure when placed in fluid communication with sample solution 30 ofhigher concentration, solvent travels across filter membrane 14 fromexchange chamber 18 into sample solution 30 until equilibrium ofconcentrations is reached. Resultantly, separator is repositionedwhereby the volume of exchange chamber 18 is reduced and the volume ofsensing chamber 20 is increased. Taking a pressure measurement afterequilibrium is established allows for calculation of the concentrationof sample solution 30.

According to embodiments, the concentration of the solute in samplesolution 30 is equal to the concentration of the solute in exchangechamber 18 when sample solution 30 and exchange chamber 18 reachequilibrium of solute concentrations.

According to embodiments, the measurement of sensor 22 is configured tocorrespond to the concentration of sample solution 30. Accordingly, themeasurement taken by sensor 22 and the concentration of sample solution30 may be expressed mathematically. The following is an example of howsuch a mathematical relationship may be determined in at least oneembodiment. The concentration of sample solution 30 may be expressed as:C_(sample)=C_(exchange)C _(exchange) =n _(exchange) /V _(exchange)where, “C” denotes a concentration, wherein “n” denotes the number ofmoles of solute, and “V” denotes a volume of the solution. Subscriptdesignations throughout denote the reference area to which each symbolrelates: “sample” for sample solution 30, “exchange” for exchangechamber 18, and “sensing” for sensing chamber 20. The formula above alsoapplies to the concentration within exchange chamber 18:

In the above equation, n_(exchange) is known and the volume of exchangechamber 18 is calculated from pressure measurements in sensing chamber20. n_(exchange) is known prior to implantation of device 10, eitherthrough direct measurement in a calibration step or by calculation basedon known concentration and volume amounts prior to implantation ofdevice 10. The amount of solute within exchange chamber 18 remainsconstant, and the change in concentration within exchange chamber 18 isattributed solely to a change in the amount of solvent. Because samplesolution 30 and exchange chamber 18 are in fluid communication, thevolume of exchange chamber 18 changes as solvent flows across filtermembrane 14 and exchange chamber 18 reaches equilibrium with theconcentration of sample solution 30.

For example, if device 10 is calibrated with a calibration solution,n_(exchange) may be calculated by bringing exchange chamber 18 intoequilibrium with the calibration solution. Because the concentration ofthe calibration solution is known and because the volume of exchangechamber may be calculated, n_(exchange) may be calculated in acalibration step. For example:

${n_{exchange} = \frac{\lbrack{CalibrationSolution}\rbrack}{V_{exchange}}}\mspace{14mu}$and$V_{exchange} = {V_{Device} - \left( \frac{P_{{sensingI}\;}V_{sensingI}}{P_{sensingF}} \right)}$${Thus},{n_{exchange} = \left( \frac{\left\lbrack {{Cal}\;{ib}\;{ra}\;{tion}\;{Solution}} \right\rbrack}{V_{Device} - \left( \frac{P_{{sensingI}\;}V_{sensingI}}{P_{sensingF}} \right)} \right)}$where P_(sensingI) and V_(sensingI) are the volume and pressure ofsensing chamber taken prior to device 10 being placed into fluidcommunication with calibration solution, and P_(sensingF) is thepressure of sensing chamber 20 after exchange chamber 18 hasequilibrated with calibration solution. These equations are mosteffective when the change in the pressure within sensing chamber 20 isrelatively small. According to embodiments, when the change reaches somecritical point, the pressure in sensing chamber 20 would be accountedfor with respect to its effect on osmotic pressure.

As equilibrium is effected, the volume of exchange chamber 18 may changeto accommodate the diffusion of solvent across filter membrane 14 intoor out of exchange chamber 18. Separator 16 is be responsive to thediffusion of solvent across filter membrane 14 by repositioning (i.e.,moving or expanding) to as the volume of exchange chamber 18 changes.The change of volume of exchange chamber 18 causes an equal and oppositechange of volume of sensing chamber 20, which can be expressed as:ΔV_(exchange)=ΔV_(sensing)

Where the total combined volume of exchange chamber 18 and sensingchamber 20 are known before implantation of device 10, this equation canbe expressed as:V _(total) =V _(exchange) +V _(sensing)where V_(total) is the total combined volume of exchange chamber 18 andsensing chamber 20. V_(total) is known and constant. Thus:V _(total) =V _(exchange) +V _(sensing)

To determine changes in the volume of exchange chamber (V_(exchange)),pressure measurements are taken, according to embodiments, and thevolume of sensing chamber is calculated, from which the volume ofsensing chamber is determined. Because the amount of solute in sensingchamber is known, the concentration of exchange chamber is calculated.Thus, because exchange chamber 18 and sample solution 30 are inequilibrium, the concentration of sample solution 30, for example theconcentration of glucose in body fluid, is known.

Sensing chamber 20 will have an initial (i) volume and pressure. Afterequilibrium is achieved with sample solution 30 and exchange chamber 18,sensing chamber will have a final (f) volume and pressure. Temperaturecalculations may be added to improve the accuracy. According to Boyle'sLaw:P_(i)V_(i)=P_(f)V_(f)

Thus, the change in the volume of sensing chamber after equilibrium isestablished is calculated as:

$V_{f} = {\frac{P_{i}V_{i}}{P_{f}}.}$

The volume of exchange chamber 18 is then expressed as:

$V_{exchange} = {{V_{Total} - V_{f}} = {V_{Total} - {\left( \frac{P_{i}V_{i}}{P_{f}} \right).}}}$

Including temperature in the equation:

$V_{exchange} = {{V_{Total} - V_{f}} = {V_{Total} - {\left( \frac{P_{i}V_{i}T_{f}}{P_{f}T_{i}} \right).}}}$

The concentration is then calculated:

$\lbrack{ExchangeChamber}\rbrack = {\frac{n_{exchange}}{V_{exchange}}.}$

According to embodiments, device 10 is configured to determineinstantaneous concentration of sample solution 30 before equilibrium ofconcentrations is achieved between sample solution 30 and exchangechamber 18. For example, the instantaneous rate of change of the volumeof exchange chamber 18 may be used to determine the solute concentrationof sample solution 30. The flux through filter membrane 14 may beproportional to the concentration gradient across filter membrane 14,wherein the flux is the amount of solvent that flows through a unit areaof filter membrane 14 per unit time and the concentration gradient isthe gradual difference in the concentration of solutes between samplesolution 30 and exchange chamber 18. Stated differently, theconcentration gradient changes at a rate proportional to that gradient.Thus, according to principles of calculus, this relationship islogarithmic, and the concentration gradient at any given time may becalculated based upon the rate of change, even before equilibrium isreached.

According to embodiments, device 10 is configured to determine physicalconditions within a patient. In at least one embodiment, device 10 isconfigured to determine the glucose concentration within an interstitialfluid. For example, the solute may be glucose, and the solvent may bewater, wherein exchange chamber contains a known amount of glucose in anaqueous solution of known volume. Filter membrane 14 may be an osmoticbarrier to allow osmosis of water across filter membrane 14 to achieveequilibrium of concentrations between sample solution 30 and exchangechamber 18. Filter membrane 14 may further prohibit diffusion of glucoseacross filter membrane 14. Those skilled in the art will appreciate thatother combinations of solutes and solvents may be applied to the presentdisclosure.

While the devices and method have been described in terms of what arepresently considered to be the most practical and embodiments, it is tobe understood that the disclosure need not be limited to the disclosedembodiments. It is intended to cover various modifications and similararrangements included within the spirit and scope of the claims, thescope of which should be accorded the broadest interpretation so as toencompass all such modifications and similar structures. The presentdisclosure includes any and all embodiments of the following claims.

The invention claimed is:
 1. A device comprising, in combination: ahousing having disposed therein a filter membrane, an exchange chamber,and a sensing chamber containing a compressible fluid and a pressuresensor adapted to measure a pressure of the compressible fluid, whereinthe filter membrane is exteriorly exposed on a perimeter of the housingand the exchange chamber is located internally of the filter membranerelative to the housing: wherein the exchange chamber and sensingchamber are separated by a movable separator that moves in response tochanges in the volume of the exchange chamber; and wherein the device isadapted to measure the concentration of a solute in a sample solutionutilizing, the measured pressure of the compressible fluid in thesensing chamber; wherein the solute is glucose, and wherein the filtermembrane provides selective fluid communication between the samplesolution and the exchange chamber, but is substantially impermeable tothe solute.
 2. The device of claim 1, wherein sample solution is a bodyfluid of an animal.
 3. The device of claim 1, wherein movement of afluid across the filter membrane causes a change in volume in theexchange chamber, the movement of the fluid occurring as the soluteconcentration in the exchange chamber equalizes with the concentrationof the solute in the sample solution.
 4. The device of claim 3, whereinthe change in volume in the exchange chamber causes movement of theseparator, which thereby effects a change in pressure in the sensingchamber.
 5. The device of claim 1, wherein the pressure sensor detectsthe change in pressure in the sensing chamber.
 6. The device of claim 1,wherein the fiber membrane is an osmotic membrane.
 7. The device ofclaim 1, further comprising a microprocessor adapted to receive inputsfrom the pressure sensor, whereby the microprocessor substantiallycalculates the concentration of the solute in the sample solution. 8.The device of claim 1, wherein the device is calibrated with a samplesolution of known concentration.
 9. The device of claim 1, wherein thehousing is implantable into a body of a patient.
 10. The device of claim1, wherein the filter membrane is adapted to be in fluid communicationwith an ambient environment surrounding the housing.
 11. A devicecomprising, in combination; a housing having disposed therein a filtermembrane, an exchange chamber, and a sensing chamber containing acompressible fluid and a pressure sensor adapted to measure a pressureof the compressible fluid, wherein the filter membrane is exteriorlyexposed on a perimeter of the housing and the exchange chamber islocated internally of the filter membrane relative to the housing;wherein the exchange chamber and sensing chamber are separated by amovable separator that moves in response to changes in the volume of theexchange chamber; and wherein the device is adapted to measure theconcentration of a solute in a sample solution utilizing the measuredpressure of the compressible fluid in the sensing chamber; wherein thesolute is glucose, and wherein movement of a fluid across the filtermembrane causes a change in volume in the exchange chamber, the movementof the fluid occurring as the solute concentration in the exchangechamber equalizes with the concentration of the solute in the samplesolution.
 12. The device of claim 11, wherein sample solution is a bodyfluid of an animal.
 13. The device of claim 11, wherein the change involume in the exchange chamber causes movement of the separator, whichthereby effects a change in pressure in the sensing chamber.
 14. Thedevice o claim 11, wherein the pressure sensor detects the change inpressure in the sensing chamber.
 15. The device of claim 11, wherein thefilter membrane is an osmotic membrane.
 16. The device of claim 11,further comprising a microprocessor adapted to receive inputs from thepressure sensor, whereby the microprocessor substantially calculates theconcentration of the solute in the sample solution.
 17. The device ofclaim 11, wherein the device is calibrated with a sample solution ofknown concentration.
 18. The device of claim 11, wherein the housing isimplantable into a body of a patient.
 19. The, device of claim 11,wherein the filter membrane is adapted to be in fluid communication withan ambient environment surrounding the housing.